Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000525926 | SCV000623976 | uncertain significance | Primary ciliary dyskinesia | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with serine at codon 3474 of the DNAH8 protein (p.Phe3474Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs538936217, ExAC 0.09%). This missense change has been observed in individual(s) with clinical features of DNAH8-related conditions (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C35"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002527662 | SCV003534193 | uncertain significance | Inborn genetic diseases | 2022-12-01 | criteria provided, single submitter | clinical testing | The c.10421T>C (p.F3474S) alteration is located in exon 70 (coding exon 69) of the DNAH8 gene. This alteration results from a T to C substitution at nucleotide position 10421, causing the phenylalanine (F) at amino acid position 3474 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |